tbuckley/cabot-search huggingface dataset:
Evaluation of Cesarean Rates for Term, Singleton, Live Vertex Deliveries in China in 2020 Among Women With No Prior Cesarean Delivery
Authors: Shaohua Yin, Lian Chen, Yubo Zhou, Pengbo Yuan, Xiaoyue Guo, Jie Lu, Lin Ge, Huifeng Shi, Xiaoxia Wang, Luyao Li, Jie Qiao, Yangyu Zhao, Hongbo Qi, Xudong Ma, Yuan Wei
Journal: JAMA Network Open (2023)

Importance Substantial regional variation in cesarean delivery rates has been reported in China, but there is a lack of reports on hospital-level variation in these rates among low-risk deliveries. Objectives To evaluate hospital variation in cesarean rates in China for term, singleton, live vertex deliveries among women with no prior cesarean delivery and to estimate contributions of individual and hospital factors. Design, Setting, and Participants This nationwide cross-sectional study used data from maternal patient discharge records collected by the Hospital Quality Monitoring System in China from January 1 to December 31, 2020. Pregnant female individuals aged 15 to 49 years (referred to hereafter as women) with at least 1 live birth were included, and low-risk deliveries were defined as term, singleton, live, vertex deliveries with no prior cesarean delivery. Exposures Birth by cesarean delivery. Main Outcomes and Measures The main outcome was cesarean delivery rate by hospital. Hierarchical logistic regression analysis was used to calculate the adjusted cesarean rate and to estimate the percentage of hospital variation in low-risk deliveries explained by individual and hospital factors. Results Among the 7 635 149 deliveries identified from 4359 hospitals in 31 provinces of mainland China, 6 599 468 (86.4%) were considered low risk. Of overall and low-risk deliveries, 3 400 162 and 2 638 097 were cesarean deliveries, corresponding to mean rates of 44.5% and 40.0%, respectively. The mean (SD) maternal age for overall and low-risk deliveries was 29.1 (4.0) and 28.8 (4.8) years, respectively, and mothers were more likely to be of Han ethnicity (89.5%). Cesarean rates varied widely among hospitals, with absolute differences between the 5th and 95th percentiles of 53.5% (19.4%-72.9%) for overall deliveries and 56.8% (14.3%-71.1%) for low-risk deliveries. Large absolute differences remained after adjusting for maternal characteristics, with rates of 47.4% (19.1%-66.5%) for overall deliveries and 52.6% (15.0%-67.6%) for low-risk deliveries. Among low-risk deliveries, hospital factors (eg, hospital province location) explained 31.3% of the hospital variation in cesarean rate and individual factors explained an additional 2.0%. Conclusions and Relevance The findings of this cross-sectional study suggest that cesarean rates varied markedly among hospitals in China in 2020, which may be attributable to hospital rather than individual factors. Future work is needed to design hospital-level initiatives to optimize cesarean use, particularly among low-risk deliveries.
<i>QuickStats</i>: Age-Adjusted Percentage* of Adults Aged ≥18 Years with Serious Psychological Distress During the Past 30 Days,† by Family Income§ — National Health Interview Survey, 2021¶
Authors: Jessly Joy, Johanna Alfier, Deepthi Kandi
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Family income, % of FPL Abbreviation: FPL = federal poverty level.* Age-adjusted percentages are based on the 2000 U.S. Census Bureau standard population, using age groups 18-44, 45-54, 55-64, 65-74, and ≥75 years, with 95% CIs indicated by error bars.† Serious psychological distress is based on responses to six questions, "During the past 30 days, how often did you feel 1) so sad that nothing could cheer you up, 2) nervous, 3) restless or fidgety, 4) hopeless, 5) that everything was an effort, or 6) worthless?"The response options "none of the time, " "a little of the time, " "some of the time, " "most of the time, " and "all of the time" were each scored from 0-4 points, respectively, and then summed for a total score ranging from 0-24 points.A value of ≥13 was used to define serious psychological distress.Only respondents who answered all six questions were included in the analysis.§ Family income groups were defined based on family income as a percentage of the federal poverty threshold.Poverty thresholds, which are published by the U.S. Census Bureau, vary by family size and the number of children in the family.Family income was imputed when missing using multiple imputation methodology.¶ Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population.In 2021, 3.8% of adults aged ≥18 years had serious psychological distress during the past 30 days.The age-adjusted percentage of adults who had serious psychological distress decreased with increasing family income, from 8.9% of adults with family income <100% of FPL, to 5.8% of adults with family income 100%-199% of FPL, to 3.8% of adults with family income 200%-399% of FPL, and to 2.0% of adults with family income ≥400% of FPL.
FDA Approval Summary: Atezolizumab as Adjuvant Treatment following Surgical Resection and Platinum-Based Chemotherapy for Stage II to IIIA NSCLC
Authors: Luckson N. Mathieu, Erin Larkins, Arup K. Sinha, Pallavi S. Mishra-Kalyani, Samina Jafri, Shyam Kalavar, Soma Ghosh, Kirsten B. Goldberg, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Clinical Cancer Research (2023)

Abstract On October 15, 2021, the FDA approved atezolizumab as adjuvant therapy in patients with stage II to IIIA non–small cell lung cancer (NSCLC) whose tumors have programmed cell death ligand 1 (PD-L1) expression on ≥1% of tumor cells (TC), as detected by an FDA-approved test. The approval was based on results from the IMpower010 trial, in which 1,005 patients with NSCLC who had completed tumor resection and cisplatin-based adjuvant chemotherapy were randomly assigned 1:1 to receive atezolizumab for 16 cycles or best supportive care. The primary endpoint of disease-free survival (DFS) as assessed by investigator was tested hierarchically in the following analysis populations: stage II–IIIA NSCLC with PD-L1 expression on ≥1% of TCs (PD-L1 ≥ 1% TC); all randomly assigned patients with stage II–IIIA NSCLC; and the intent-to-treat population comprising all randomly assigned patients. At the prespecified interim DFS analysis, IMpower010 demonstrated a statistically significant and clinically meaningful improvement in DFS in the stage II–IIIA PD-L1 ≥ 1% TC analysis population, with an HR of 0.66 (95% confidence interval, 0.50–0.88; P = 0.004) favoring the atezolizumab arm. The safety profile of atezolizumab was generally consistent with known toxicities of anti–PD-(L) antibodies. The VENTANA PD-L1 (SP263) Assay (Ventana Medical Systems, Inc.) was contemporaneously approved as a companion diagnostic device to select patients with NSCLC who are PD-L1 ≥ 1% TC for adjuvant treatment with atezolizumab. Atezolizumab is the first immune checkpoint inhibitor approved by FDA for the adjuvant treatment of NSCLC.
Tick-borne encephalitis virus IgG antibody surveillance: vaccination- and infection-induced seroprevalences, south-western Germany, 2021
Authors: Kathrin Euringer, Philipp Girl, Klaus Kaier, Jan Peilstöcker, Michael Schmidt, Michael Müller-Steinhardt, Beate Rauscher, Evelyn Bressau, Winfried V Kern, Gerhard Dobler, Johannes P Borde
Journal: Eurosurveillance (2023)

BackgroundThe exact epidemiology of tick-borne encephalitis virus (TBEV) infections is unknown because many TBEV infections have an influenza-like or asymptomatic course. Surveillance data are based on patients with any (predominantly neurological) symptoms that prompted diagnostic testing. Infection- and vaccine-induced antibodies against TBEV can be distinguished using an NS1 IgG ELISA.AimIn a seroprevalence study we aimed to investigate TBEV antibody prevalence, incidences, manifestation indices and potential protection rates in a highly endemic district in south-western Germany.MethodsWe analysed 2,220 samples from healthy blood donors collected between May and September 2021. The reported number of TBEV infections was provided on a sub-district level by the local public health authorities. Blood samples were first screened using a TBEV IgG ELISA. In a second step, all positive samples were further analysed with a recently established NS1 IgG ELISA. The presence of specific antibodies against TBEV (excluding cross-reacting antibodies against other flaviviruses) was confirmed by testing screening-positive samples with a microneutralisation assay.ResultsOf 2,220 included samples, 1,257 (57%) tested positive by TBEV IgG ELISA and 125 tested positive for infection-induced TBEV NS1 antibodies, resulting in a TBEV NS1 IgG seroprevalence at 5.6% in our population. The yearly incidence based on the NS1 ELISA findings resulted in 283 cases per 100,000 inhabitants.ConclusionUsing the TBEV NS1 IgG assay, we confirmed a manifestation index of ca 2% and a high incidence of predominantly silent TBEV infections (> 250/100,000/year), which exceeds the incidence of notified cases (4.7/100,000/year) considerably.
Prognostic Value of Microscopic Tumor Necrosis in Adrenal Cortical Carcinoma
Authors: Michaela Luconi, Giulia Cantini, Rachel S. van Leeuwaarde, Rogina Roebaar, Laura Fei, Arianna Pia Propato, Raffaella Santi, Tonino Ercolino, Massimo Mannelli, Letizia Canu, Ronald R. de Krijger, Gabriella Nesi
Journal: Endocrine Pathology (2023)

Abstract Adrenal cortical carcinoma (ACC) is an uncommon neoplasm with variable prognosis. Several histologic criteria have been identified as predictors of malignancy in adrenal cortical tumors. The Weiss score is the system most widely employed for diagnostic purposes, but also possesses prognostic value. We aim to determine the relative impact of each Weiss parameter on ACC patient survival. A multicenter retrospective analysis was conducted on a series of 79 conventional ACCs surgically treated at the Florence and Utrecht centers of the European Network for the Study of Adrenal Tumors (ENSAT). Weiss classification was recapitulated using principal component analysis (PCA). The Kaplan–Meier and Cox multivariate regression analyses were applied in order to estimate the prognostic power of Weiss versus other clinical parameters. PCA reduced the nine Weiss parameters to the best fitting 4-component model, each parameter clustering with a single component. Necrosis and venous invasion clustered together with the highest scores, thus establishing the most relevant component (Component 1) to explain Weiss distribution variability. Only Component 1 significantly predicted overall survival (OS, log-rank = 0.008) and disease-free survival (DFS, log-rank &lt; 0.001). When considering the prognostic power of Weiss parameters, necrosis alone could independently assess OS (log-rank = 0.004) and DFS (log-rank &lt; 0.001) at both the Kaplan–Meier and multivariate Cox regression analyses [hazard ratio (HR) = 7.8, 95% confidence interval [CI] = 1.0–63.5, p = 0.05, and HR = 12.2, 95% CI = 1.6–95.0, p = 0.017, respectively]. The presence of necrosis significantly shortened time to survival (TtS) and time to recurrence (TtR), 57.5 [31.5–103.5] vs 34 [12–78] months ( p = 0.05) and 57.5 [31.5–103.5] vs 7 [1.0–31.5] months ( p &lt; 0.001), respectively. Our study suggests that, of the Weiss parameters, necrosis is the most powerful adverse factor and the best predictor of OS and DFS in ACC patients.
Disparities in Survival Due to Social Determinants of Health and Access to Treatment in US Patients With Operable Malignant Pleural Mesothelioma
Authors: Ahmed Alnajar, Samuel A. Kareff, Syed S. Razi, J. Sunil Rao, Gilberto De Lima Lopes, Dao M. Nguyen, Nestor Villamizar, Estelamari Rodriguez
Journal: JAMA Network Open (2023)

Importance Outcomes of localized malignant pleural mesothelioma (MPM) remain poor despite multimodality therapy. It is unclear what role disparities have in the overall survival (OS) of patients with operable MPM. Objective To examine survival disparities associated with social determinants of health (SDOHs) and treatment access in patients with malignant pleural mesothelioma. Design, Setting, and Participants In this observational, retrospective cohort study, patients with MPM diagnosed between January 1, 2004, and December 31, 2017, were identified from the National Cancer Database with a maximum follow-up time of 13.6 years. The analysis was conducted from February 16, 2022, to July 29, 2022. Patients were included if they were diagnosed with potentially resectable clinical stage I to IIIA MPM, had epithelioid and biphasic histologic subtypes, and received chemotherapy. Patients were excluded if they could not receive curative surgery, were 75 years or older, or had metastasis, unknown stage, or tumor extension to the chest wall, mediastinal tissues, or organs. Exposures Chemotherapy alone vs chemotherapy with curative surgery in the form of pleurectomy and decortication or extrapleural pneumonectomy. Main Outcomes and Measures The primary end point was OS. Cox proportional hazards regression models were used to determine hazard ratios (HRs) for OS, including univariable and multivariable models controlling for potential confounders, including demographic, comorbidity, clinical, treatment, tumor, and hospital-related variables, as well as SDOHs. Results A total of 1389 patients with MPM were identified (median [IQR] age, 66 [61-70] years; 1024 [74%] male; 12 [1%] Asian, 49 [3%] Black, 74 [5%] Hispanic, 1233 [89%] White, and 21 [2%] of other race). The median OS was 1.7 years (95% CI, 1.6-1.8). Risk factors associated with worse OS included older age, male sex, Black race, low income, and low educational attainment. Factors associated with greater odds of survival included receipt of surgical therapy, recent year of treatment, increased distance to travel, and treatment at high-volume academic hospitals. The risk factors most strongly associated with poor OS included Black race (HR, 1.96; 95% CI, 1.43-2.69) and male sex (HR, 1.60; 95% CI, 1.38-1.86). Surgical treatment in addition to systemic chemotherapy (HR, 0.70; 95% CI, 0.61-0.81) was independently associated with improved OS, as were chemotherapy initiation (HR, 0.93; 95% CI, 0.87-0.99) and greater travel distance from the hospital (HR, 0.92; 95% CI, 0.86-0.98). Conclusions and Relevance In this retrospective cohort study of patients with operable MPM, there was significant variability in access to care by SDOHs. Addressing disparities in access to multimodality therapy can help ensure equity of care for patients with MPM.
While Waiting for a Randomized Clinical Trial of Nirmatrelvir for Prevention of Post–COVID-19 Condition
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2023)

Vasiliki Tsampasian, MD, MSc; Hussein Elghazaly, MBBS; Rahul Chattopadhyay, MBBS, MSc; Maciej Debski, MD, PhD; Thin Kyi Phyu Naing, MBBS; Pankaj Garg, PhD; Allan Clark, PhD; Eleana Ntatsaki, MD(Res), MA; Vassilios S. Vassiliou, MBBS, PhD
An Oncology Artificial Intelligence Fact Sheet for Cancer Clinicians
Authors: Danielle S. Bitterman, Aqdas Kamal, Raymond H. Mak
Journal: JAMA Oncology (2023)

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Memory T cells possess an innate-like function in local protection from mucosal infection
Authors: Tanvi Arkatkar, Veronica Davé, Irene Cruz Talavera, Jessica B. Graham, Jessica L. Swarts, Sean M. Hughes, Timothy A. Bell, Pablo Hock, Joe Farrington, Ginger D. Shaw, Anna Kirby, Michael Fialkow, Meei-Li Huang, Keith R. Jerome, Martin T. Ferris, Florian Hladik, Joshua T. Schiffer, Martin Prlic, Jennifer M. Lund
Journal: Journal of Clinical Investigation (2023)

Mucosal infections pose a significant global health burden. Antigen-specific tissue-resident T cells are critical to maintaining barrier immunity. Previous studies in the context of systemic infection suggest that memory CD8+ T cells may also provide innate-like protection against antigenically unrelated pathogens independent of T cell receptor engagement. Whether bystander T cell activation is also an important defense mechanism in the mucosa is poorly understood. Here, we investigated whether innate-like memory CD8+ T cells could protect against a model mucosal virus infection, herpes simplex virus 2 (HSV-2). We found that immunization with an irrelevant antigen delayed disease progression from lethal HSV-2 challenge, suggesting that memory CD8+ T cells may mediate protection despite the lack of antigen specificity. Upon HSV-2 infection, we observed an early infiltration, rather than substantial local proliferation, of antigen-nonspecific CD8+ T cells, which became bystander-activated only within the infected mucosal tissue. Critically, we show that bystander-activated CD8+ T cells are sufficient to reduce early viral burden after HSV-2 infection. Finally, local cytokine cues within the tissue microenvironment after infection were sufficient for bystander activation of mucosal tissue memory CD8+ T cells from mice and humans. Altogether, our findings suggest that local bystander activation of CD8+ memory T cells contributes a fast and effective innate-like response to infection in mucosal tissue.
Epithelial talin-1 protects mice from <i>Citrobacter rodentium</i> -induced colitis by restricting bacterial crypt intrusion and enhancing T cell immunity
Authors: Yvonne L. Latour, Margaret M. Allaman, Daniel P. Barry, Thaddeus M. Smith, Kamery J. Williams, Kara M. McNamara, Justin Jacobse, Jeremy A. Goettel, Alberto G. Delgado, M. Blanca Piazuelo, Shilin Zhao, Alain P. Gobert, Keith T. Wilson
Journal: Gut Microbes (2023)

Pathogenic enteric Escherichia coli present a significant burden to global health. Food-borne enteropathogenic E. coli (EPEC) and Shiga toxin-producing E. coli (STEC) utilize attaching and effacing (A/E) lesions and actin-dense pedestal formation to colonize the gastrointestinal tract. Talin-1 is a large structural protein that links the actin cytoskeleton to the extracellular matrix though direct influence on integrins. Here we show that mice lacking talin-1 in intestinal epithelial cells (Tln1Δepi) have heightened susceptibility to colonic disease caused by the A/E murine pathogen Citrobacter rodentium. Tln1Δepi mice exhibit decreased survival, and increased colonization, colon weight, and histologic colitis compared to littermate Tln1fl/fl controls. These findings were associated with decreased actin polymerization and increased infiltration of innate myeloperoxidase-expressing immune cells, confirmed as neutrophils by flow cytometry, but more bacterial dissemination deep into colonic crypts. Further evaluation of the immune population recruited to the mucosa in response to C. rodentium revealed that loss of Tln1 in colonic epithelial cells (CECs) results in impaired recruitment and activation of t cells. C. rodentium infection-induced colonic mucosal hyperplasia was exacerbated in Tln1Δepi mice compared to littermate controls. We demonstrate that this is associated with decreased CEC apoptosis and crowding of proliferating cells in the base of the glands. Taken together, talin-1 expression by CECs is important in the regulation of both epithelial renewal and the inflammatory t cell response in the setting of colitis caused by C. rodentium, suggesting that this protein functions in CECs to limit, rather than contribute to the pathogenesis of this enteric infection.
A One Health approach revealed the long-term role of Mycobacterium caprae as the hidden cause of human tuberculosis in a region of Spain, 2003 to 2022
Authors: Miguel Martínez-Lirola, Marta Herranz, Sergio Buenestado Serrano, Cristina Rodríguez-Grande, Eva Dominguez Inarra, Jose Antonio Garrido-Cárdenas, Ana María Correa Ruiz, María Pilar Bermúdez, Manuel Causse del Río, Verónica González Galán, Julia Liró Armenteros, Jose María Viudez Martínez, Silvia Vallejo-Godoy, Ana Belén Esteban García, María Teresa Cabezas Fernández, Patricia Muñoz, Laura Pérez Lago, Darío García de Viedma
Journal: Eurosurveillance (2023)

IntroductionMycobacterium caprae is a member of the Mycobacterium tuberculosis complex (MTBC) not routinely identified to species level. It lacks specific clinical features of presentation and may therefore not be identified as the causative agent of tuberculosis. Use of whole genome sequencing (WGS) in the investigation of a family microepidemic of tuberculosis in Almería, Spain, unexpectedly identified the involvement of M. caprae.AimWe aimed to evaluate the presence of additional unidentified M. caprae cases and to determine the magnitude of this occurrence.MethodsFirst-line characterisation of the MTBC isolates was done by MIRU-VNTR, followed by WGS. Human and animal M. caprae isolates were integrated in the analysis.ResultsA comprehensive One Health strategy allowed us to (i) detect other 11 M. caprae infections in humans in a period of 18 years, (ii) systematically analyse M. caprae infections on an epidemiologically related goat farm and (iii) geographically expand the study by including 16 M. caprae isolates from other provinces. Integrative genomic analysis of 41 human and animal M. caprae isolates showed a high diversity of strains. The animal isolates' diversity was compatible with long-term infection, and close genomic relationships existed between isolates from goats on the farm and recent cases of M. caprae infection in humans.DiscussionZoonotic circulation of M. caprae strains had gone unnoticed for 18 years. Systematic characterisation of MTBC at species level and/or extended investigation of the possible sources of exposure in all tuberculosis cases would minimise the risk of overlooking similar zoonotic events.
IL-18–secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models
Authors: Janneke E. Jaspers, Jonathan F. Khan, William D. Godfrey, Andrea V. Lopez, Metamia Ciampricotti, Charles M. Rudin, Renier J. Brentjens
Journal: Journal of Clinical Investigation (2023)

Patients with small cell lung cancer (SCLC) generally have a poor prognosis and a median overall survival of only about 13 months, indicating the urgent need for novel therapies. Delta-like protein 3 (DLL3) has been identified as a tumor-specific cell surface marker on neuroendocrine cancers including SCLC. In this study, we developed a chimeric antigen receptor (CAR) against DLL3 that displays antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of the proinflammatory cytokine interleukin-18 (IL-18) greatly enhanced the potency of DLL3-targeting CAR T cell therapy. In a murine metastatic SCLC model, IL-18 production increased the activation of both CAR T cells and endogenous tumor-infiltrating lymphocytes. We also observed an increased infiltration, repolarization and activation of antigen-presenting cells. Lastly, human IL-18-secreting anti-DLL3 CAR T cells showed an increased memory phenotype, less exhaustion and induced durable responses in multiple SCLC models, an effect that could be further enhanced with anti-PD-1 blockade. Together, these results define DLL3-targeting CAR T cells that produce IL-18 as a promising novel strategy against DLL3-expressing solid tumors.